25-Hydroxycholesterol Protects Host against Zika Virus Infection and Its Associated Microcephaly in a Mouse Model.

Li C1, Deng YQ2, Wang S3, Ma F4, Aliyari R5, Huang XY2, Zhang NN6, Watanabe M7, Dong HL2, Liu P8, Li XF2, Ye Q2, Tian M9, Hong S3, Fan J3, Zhao H2, Li L8, Vishlaghi N7, Buth JE7, Au C5, Liu Y8, Lu N8, Du P8, Qin FX10, Zhang B11, Gong D12, Dai X12, Sun R12, Novitch BG13, Xu Z14, Qin CF15, Cheng G16

Immunity. 2017 Mar 21;46(3):446-456.

PMID: 28314593  DOI: 10.1016/j.immuni.2017.02.012

Abstract
Zika virus (ZIKV) has become a public health threat due to its global transmission and link to severe congenital disorders. The host immune responses to ZIKV infection have not been fully elucidated, and effective therapeutics are not currently available. Herein, we demonstrated that cholesterol-25-hydroxylase (CH25H) was induced in response to ZIKV infection and that its enzymatic product, 25-hydroxycholesterol (25HC), was a critical mediator of host protection against ZIKV. Synthetic 25HC addition inhibited ZIKV infection in vitro by blocking viral entry, and treatment with 25HC reduced viremia and conferred protection against ZIKV in mice and rhesus macaques. 25HC suppressed ZIKV infection and reduced tissue damage in human cortical organoids and the embryonic brain of the ZIKV-induced mouse microcephaly model. Our findings highlight the protective role of CH25H during ZIKV infection and the potential use of 25HC as a natural antiviral agent to combat ZIKV infection and prevent ZIKV-associated outcomes, such as microcephaly.